Screening of potential biomarkers for distinguishing between latent and active tuberculosis in children using bioinformatics analysis

摘要

Tuberculosis (TB) isachronicinfectious diseasecaused bymycobacteriumtuberculosis (M.tb). Globally, it has the highestmortality rateamong single pathogens. WhenM.tb invades the host, it reproduces in theresidentsiteand causes infection, triggering innateimmunity. Various innate immunecells, such as macrophagesand dendriticcells,etc. furtheractivatespecific T cellimmuneresponse by regulating effectorsand signaling pathways, thereby killingM.tb and preventing its replication. [1,2] Among them, most ofM.tb will beswallowed bymacrophages, which could recruit other immunecells to gather organized and formgranulomatous lesions to curb thereproduction ofM.tb, but the granulation tissuecannot completely eradicate M.tb. [3] At this point, theinfectionmay becomestationary or dormantand isconsidered latent tuberculosis infection (LTBI). Underconditions offailing immunesurveillance,approximately 5%to 10%ofinfected individuals will develop active TBduring their lifetime. [4] Dueto the diversity of potentialstatesand outcomes, wecurrently lack reliable methods to identify people who might develop active TB. [5,6] Previous studies have mainly focused on the development of newdiagnostictools foradult tuberculosis, whilechildhood TBhas relatively been neglected. For mostchildhood cases, the detection rateisabout 35%dueto lack ofeffective diagnostic methodsespecially in early-stage TBand in somecases, thesmearsand cultures givefalse positivesand negatives. [7,8] One ofthe uniquefeatures ofchildhood TBis its speedy development into the disease which typically occurs within thefirst year following infection because oftheimmatureimmunesystem. This is unlikein adults whereanM.tb infection could last for decades without worsening. [9] Although extensive preclinicalresearchmodels haveachieved encouraging results in the diagnosis, treatment,and immunological pathogenesis ofTB, none ofthemcould perfectly summarize human tuberculosis syndrome. [3,10] Therefore, thereisan urgent need to explore potential biomarkers for usein distinguishing betweenLTBIand active TBin children forearly and accurate diagnosisand treatment.